Porcine Reproductive and Respiratory Syndrome (PRRS) is a viral disease of swine that causes the greatest annual economic loss compared to any current or previous infectious disease that has ever afflicted the pork industry. PRRS, also known as “Mystery Swine Disease,” Swine Infertility and Respiratory Syndrome (SIRS), and “Blue Ear Disease,” was first detected in North America in 1987 and in Europe in 1990. Since then, PRRS has since become a major threat to swine industries in most pig-producing areas throughout the world, except Australia. PRRS has its most pronounced effect on young and newborn piglets. Up to 20-30% of the piglets in the litters from infected sows are stillborn, and up to 80% of piglets in infected herds die before weaning. The economic consequences of the disease, accordingly, are devastating (see U.S. Pat. No. 5,476,778 by Chladek et al.). In a study funded in part by the National Pork Board, it was noted that losses attributed to PRRS exceeded $560M in the United States alone (Neumann E J et al., 2005).
The research of PRRS and development of diagnostic and therapeutic approaches, including new vaccines and vaccine production technology, is constrained by the restricted availability of options for culturing the PRRS virus in vitro. Previously, simian cells have been the only type of available cell line known to sustain growth of PRRS for vaccine production. The simian cell line MA-104 and related derivatives (e.g., MARC-145) may represent what until now might have been the only practical option for supporting PRRS virus replication in vitro.
The present invention improves the state of the art by providing alternative options for working with PRRS virus such as the embodiment of non-simian cells that can support PRRS growth.
Other approaches have been taken, with less than desirable outcomes, to develop options for growth of PRRSV. In one approach, porcine alveolar macrophages can be used for PRRSV growth; however, the high degree of inherent variability in cells isolated from different pigs is considered a disadvantage (see Vincent et al., 2005; Bautista et al., 1993). In another approach, Weingartl et al. established porcine monomyeloid cell lines following transfection of primary porcine alveolar macrophages obtained from 12-week-old pigs. Those cells were tested but failed to support replication of PRRSV (Weingartl et al., 2002, Journal of Virological Methods 104:203-216). In contrast the present invention surprisingly discloses, inter alia, the discovery that certain cells from fetal pigs are indeed capable of supporting PRRSV growth.
Technology applications of great interest for utilization of the present invention include applied research aspects such as veterinary vaccine production in addition to the ability to study the growth of the PRRS virus at the basic research level. Vaccines for PRRSV which are modified live vaccines or inactivated killed/vaccines can be produced by the cells and cell lines of the invention. A tool to grow this particular virus and related methods also are significant in the context of generating material useful for diagnostic applications. In the context of a historical analogy intended to emphasize breakthrough science, the ability to work with human immunodeficiency virus (HIV) was generally stifled due to difficulties and a lack of options for culturing the virus in vitro. Crucial advances in the ability to study and generate diagnostics and potential vaccines for HIV related to the watershed event of being able to successfully culture the virus in vitro; see Gallo R C, 2002, Historical essay. The early years of HIV/AIDS; Science 298(5599):1728-30.
The major limitation to the control of PRRS disease is believed to rest with the availability and efficacy of vaccine technologies. The contribution of innovative cells and methods for growth of PRRS virus thus represents a significant advance in the ability to work with PRRS virus, to develop alternative and/or improved vaccine technologies, and to address the problem of PRRS disease.